This proposal seeks funding for the Molecular Mechanisms of Disease (MMoD) predoctoral training program at the University of Nebraska-Lincoln. The MMoD program addresses the NIH training focus of Cellular, Biochemical, and Molecular Sciences by providing advanced training and career development in biomedical research centered on molecular interactions and chemical transformations. The goal of the program is to develop outstanding new scientists who work in collaborative multi-disciplinary teams to research disease mechanisms using quantitative approaches that ultimately yield tangible strategies for prevention and therapy. To accomplish this goal, the program will recruit high-quality, motivated predoctoral trainees with a strong interest in the underlying causes of human disease and engage them in mentored, cutting-edge research. The MMoD program will (1) Provide a rigorous curriculum and innovative, collaborative research opportunities for six predoctoral trainees per year (NIH-supported) to become experts in the mechanistic study of human disease; (2) Cultivate an interactive training environment that enables trainees to develop professional skills in communication, leadership, proposal-writing, scholarship, entrepreneurship, and teaching; and 3) Build a cohort of trainees from diverse perspectives that have the knowledge and ability to work at the crossroads of different disciplines in their future careers as PhD scientists. The MMoD program provides collaborative training in mechanistic disease research in the areas of molecular signaling, metabolic integrity, oxidative stress and redox biology, and disease microenvironment. The MMoD mentoring team spans seven departments and three colleges and includes 32 faculty members from early-stage to established investigators with strong histories in biomedical research funding and graduate student mentoring. Trainees will conduct four research rotations in year 1 before choosing a faculty mentor, and will be supported by NIH T32 funding for up to two years beginning in the second year of their five-year program. Selection of new trainees for NIH support will be competitive, based on strong academic record, research progress and potential, and an original collaborative proposal bridging disciplinary boundaries for innovative thesis research. Trainees will take a flexible core curriculum that includes a course on Metabolic Function and Dysfunction, and a quantitative biology course and two macromolecules courses from an approved core. Though these courses and MMoD training modules, students will acquire skills in evidence-based education, quantitative and critical analysis, and, rigor and reproducibility in research. They will also have opportunities for professional experiences related to intellectual property and the pharmaceutical industry in preparation for potential career options. The MMoD program provides a framework that enables trainees to gain a broad knowledge base; actively seek research collaborations; produce an outstanding record of original published research; and develop presentation, proposal-writing, and leadership skills that will position them for future excellence as independent researchers.